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FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs
Health span is driven by a precise interplay between genes and the environment. Cell response to environmental cues is mediated by signaling cascades and genetic variants that affect gene expression by regulating chromatin plasticity. Indeed, they can promote the interaction of promoters with regula...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Research Network of Computational and Structural Biotechnology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606898/ https://www.ncbi.nlm.nih.gov/pubmed/31303978 http://dx.doi.org/10.1016/j.csbj.2019.06.011 |
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author | Sanese, Paola Forte, Giovanna Disciglio, Vittoria Grossi, Valentina Simone, Cristiano |
author_facet | Sanese, Paola Forte, Giovanna Disciglio, Vittoria Grossi, Valentina Simone, Cristiano |
author_sort | Sanese, Paola |
collection | PubMed |
description | Health span is driven by a precise interplay between genes and the environment. Cell response to environmental cues is mediated by signaling cascades and genetic variants that affect gene expression by regulating chromatin plasticity. Indeed, they can promote the interaction of promoters with regulatory elements by forming active chromatin hubs. FOXO3 encodes a transcription factor with a strong impact on aging and age-related phenotypes, as it regulates stress response, therefore affecting lifespan. A significant association has been shown between human longevity and several FOXO3 variants located in intron 2. This haplotype block forms a putative aging chromatin hub in which FOXO3 has a central role, as it modulates the physical connection and activity of neighboring genes involved in age-related processes. Here we describe the role of FOXO3 and its single-nucleotide polymorphisms (SNPs) in healthy aging, with a focus on the enhancer region encompassing the SNP rs2802292, which upregulates FOXO3 expression and can promote the activity of the aging hub in response to different stress stimuli. FOXO3 protective effect on lifespan may be due to the accessibility of this region to transcription factors promoting its expression. This could in part explain the differences in FOXO3 association with longevity between genders, as its activity in females may be modulated by estrogens through estrogen receptor response elements located in the rs2802292-encompassing region. Altogether, the molecular mechanisms described here may help establish whether the rs2802292 SNP can be taken advantage of in predictive medicine and define the potential of targeting FOXO3 for age-related diseases. |
format | Online Article Text |
id | pubmed-6606898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Research Network of Computational and Structural Biotechnology |
record_format | MEDLINE/PubMed |
spelling | pubmed-66068982019-07-12 FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs Sanese, Paola Forte, Giovanna Disciglio, Vittoria Grossi, Valentina Simone, Cristiano Comput Struct Biotechnol J Review Article Health span is driven by a precise interplay between genes and the environment. Cell response to environmental cues is mediated by signaling cascades and genetic variants that affect gene expression by regulating chromatin plasticity. Indeed, they can promote the interaction of promoters with regulatory elements by forming active chromatin hubs. FOXO3 encodes a transcription factor with a strong impact on aging and age-related phenotypes, as it regulates stress response, therefore affecting lifespan. A significant association has been shown between human longevity and several FOXO3 variants located in intron 2. This haplotype block forms a putative aging chromatin hub in which FOXO3 has a central role, as it modulates the physical connection and activity of neighboring genes involved in age-related processes. Here we describe the role of FOXO3 and its single-nucleotide polymorphisms (SNPs) in healthy aging, with a focus on the enhancer region encompassing the SNP rs2802292, which upregulates FOXO3 expression and can promote the activity of the aging hub in response to different stress stimuli. FOXO3 protective effect on lifespan may be due to the accessibility of this region to transcription factors promoting its expression. This could in part explain the differences in FOXO3 association with longevity between genders, as its activity in females may be modulated by estrogens through estrogen receptor response elements located in the rs2802292-encompassing region. Altogether, the molecular mechanisms described here may help establish whether the rs2802292 SNP can be taken advantage of in predictive medicine and define the potential of targeting FOXO3 for age-related diseases. Research Network of Computational and Structural Biotechnology 2019-06-13 /pmc/articles/PMC6606898/ /pubmed/31303978 http://dx.doi.org/10.1016/j.csbj.2019.06.011 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Article Sanese, Paola Forte, Giovanna Disciglio, Vittoria Grossi, Valentina Simone, Cristiano FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs |
title | FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs |
title_full | FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs |
title_fullStr | FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs |
title_full_unstemmed | FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs |
title_short | FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs |
title_sort | foxo3 on the road to longevity: lessons from snps and chromatin hubs |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606898/ https://www.ncbi.nlm.nih.gov/pubmed/31303978 http://dx.doi.org/10.1016/j.csbj.2019.06.011 |
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